Journal of Neuroinflammation最新文献

Chronic periodontitis is increasingly recognized as a potential upstream contributor to neurodegenerative processes through sustained systemic inflammation, microbial dysbiosis, and blood-brain barrier (BBB) alterations. This review synthesizes human and experimental evidence linking periodontal pathogens-including but not limited to Porphyromonas gingivalis as well as broader dysbiotic consortia such as Tannerella forsythia, Treponema denticola, and other keystone oral taxa-to neuroinflammatory cascades associated with cognitive decline. Mechanistic insights highlight the roles of glial activation, proinflammatory cytokines, and polymicrobial virulence-mediated neuronal stress in bridging oral and brain pathology, while age-related factors such as immunosenescence and microbiome imbalance amplify systemic vulnerability. Human biomarker and imaging studies support an association between chronic periodontal inflammation and neurovascular dysfunction, suggesting that oral disease may act as a persistent peripheral amplifier of central immune activation. Recent research has expanded into biomarker discovery and translational implementation, yet progress remains limited by population heterogeneity, methodological variability, and regulatory complexity. Promising interventions-including anti-inflammatory therapies, oral hygiene optimization, probiotic or dietary modulation, and molecular strategies such as polymicrobial-targeted approaches, gingipain inhibition, and microRNA-based modulation-are discussed within emerging multi-omics and precision-medicine frameworks. Although standardization and longitudinal validation are still required, integrative approaches combining inflammatory, microbial, and genetic profiling may enable individualized risk assessment and targeted prevention. As global populations age, addressing the oral-brain axis offers a practical and modifiable pathway to lessen the burden of neurodegenerative diseases and support healthier cognitive aging.

Background: Modulating harmful neuroimmune responses is a promising therapeutic approach for hemorrhagic stroke, a condition that still lacks effective treatment. The immune checkpoint B and T Lymphocyte Attenuator (BTLA) helps suppress immune activation; however, its role in intracerebral hemorrhage (ICH) remains unclear. This study explores whether a BTLA-activating antibody can reduce neuroinflammation, mitigate brain injury, improve recovery after ICH, and elucidate the underlying mechanisms.

Methods: An ICH model was generated in male C57BL/6 mice by stereotactic injection of collagenase VII-S into the left striatum. The mice received intraperitoneal administration of an agonistic anti-BTLA antibody to serve as a BTLA agonist. Therapeutic effects were evaluated using a multimodal approach that included flow cytometry, Western blotting, immunofluorescence staining, histological examination, and behavioral tests. Additionally, microglial depletion was performed by feeding the CSF1R inhibitor PLX5622.

Results: Our findings demonstrate that a single dose of an agonistic anti-BTLA antibody, administered 30 min post-ICH, significantly reduced the infiltration of CD45^high, CD3⁺, and CD3⁺CD4⁺ immunocytes, as well as the activation of CD3⁺CD4⁺ and CD3⁺CD8⁺ immunocytes, in the hemorrhagic brain following acute ICH. Simultaneously, it reduced neutrophil infiltration into the hemorrhagic brain and suppressed the activation of peripheral CD3⁺CD8⁺ immune cells. It also alleviated molecular and cellular neuroinflammation in the hemorrhagic brain during the early phase after ICH. These effects in the brain of adult male mice ultimately reduced both acute-phase brain injury volume and long-term residual lesions, while facilitating neurological recovery. However, microglial depletion abolished the anti-inflammatory effects of the agonistic anti-BTLA antibody, indicating that its action is contingent on microglia-mediated immunomodulation.

Conclusion: The agonistic anti-BTLA antibody significantly attenuates neuroinflammation and reduces brain injury following ICH, accompanied by enhanced neurological recovery. This protective effect appears to be mediated through microglia-dependent mechanisms. Our findings highlight BTLA may be a novel and promising immunomodulatory target for the treatment of ICH.

Mild hypoxia is a common condition encountered in various situations, such as high-altitude living, respiratory diseases, anaemia, and certain cardiovascular disorders. At the same time, mild hypoxia often goes unnoticed and can lead to long-term brain impairments. Understanding the subtle effects of mild hypoxia on the brain is essential for early diagnosis and intervention to prevent serious neurological and psychiatric complications. The pathophysiology of mild chronic hypoxia is complex; nevertheless, based on the literature, two main pathways can be distinguished. The first involves the direct effects of mild hypoxia on the brain and spinal cord, while the second involves the influence of enhanced systemic inflammation. In this narrative review, we discuss the current understanding of the effects of mild hypoxia on brain metabolism, cellular models, perfusion, the blood-brain barrier (BBB), the blood-spinal cord barrier (BSCB) and the brain-cerebrospinal fluid barrier (BCSFB). We explore the intricate relationship between peripheral inflammation induced by hypoxia and the BBB/BSCB/BCSFB, shedding light on the underlying mechanisms and their potential implications for central nervous system health.